Distinguishing acupuncture from placebo acupuncture has been a methodological challenge. We propose to move this question into a well-controlled mechanistic laboratory model using a quantitative brain imaging method (fMRI) to investigate the neurobiological mechanism of acupuncture analgesia, placebo analgesia and their interrelationship. A well tested method to induce high expectation and low expectation will be combined with acupuncture analgesia and sham acupuncture analgesia to create a 2 X 2 neuroimaging comparison of verum (real) acupuncture and sham acupuncture each paired with positive and negative expectancies. To delineate the different brain networks involved, we will compare pre- and post-treatment fMRI signal changes induced by application of calibrated noxious stimuli (pain sensory encoding) and a subsequent rating task (pain intensity evaluation) after the different treatments. We hypothesize that modulation of the pain intensity evaluation process is a critical substrate of placebo analgesia. Specifically, we hypothesize that expectancy (placebo) analgesia, which critically depends on former knowledge, belief or experience, will be initialized by activity in the central nervous system. We propose that the activity in this network of brain regions will produce analgesia by activating descending endogenous opioid systems as well as by activating what we have called the "selective pain intensity evaluation distortion process". The first mechanism may also be shared with acupuncture analgesia, however, the second mechanism should be unique for placebo analgesia in our study population who have no prior experience or expectancy for acupuncture analgesia. This proposal is directly relevant to a recent Program Announcement (PA-03-125) that calls for "biobehavioral pain research". This proposal is also relevant to a recent RFA (AT-02-002) that calls for "An Integrative Approach to Elucidation of the Underlying Mechanisms of Placebo Effect". It is also relevant to FY 2003 Research Priorities that call for "preclinical neurobiological studies of the mechanisms underlying CAM approaches to the management of acute or chronic pain".